Emails. It’s a love – hate relationship. We loathe a full inbox when returning from vacation because those emails represent how far behind we are with our work. Even during normal business hours, nonstop emails can draw our attention when we are trying to close out our workday. It can be hard to turn off the information flow.
On the other hand, emails have become a convenient and expedient way to communicate with others. Emails allow us to deliver valuable study information rapidly across sponsors, CROs, study sites, and vendors. Much of our clinical trial work is accomplished via email. Now, in this sudden era of the COVID-19 pandemic, we are going to rely even more on email and other virtual technologies to keep us moving forward.
Correspondence is an important component in reconstructing how a trial was conducted. Clinical trial teams generate a tremendous amount of correspondence. While it’s easy to define letters, team meeting agendas, meeting minutes, and telephone call reports as “relevant” correspondence (to use the FDA’s term in ICH E6(R2)), what about all those emails? Surely, they don’t all belong in the TMF! It can be very confusing. Some studies ask all team members to save every email, and while some sponsors may have other business reasons for saving all project related email, what do regulatory agencies want in the TMF?
In a 2012 GCP Forum, the MHRA acknowledged the email dilemma stating that “some CRO organizations rely solely on email correspondence to confirm sponsor approval of processes, documents, and decisions.” The MHRA stated that:
“Only relevant correspondence that is necessary for reconstruction of key activities and decisions (for example, the medical monitor allows an ineligible subject to remain in the trial) or that contains other significant information must be retained. If some correspondence is not retained (particularly certain emails which may not add any value by being retained, such as, email correspondence between investigator site staff and the trial monitor discussing holidays or suitable hotels to stay in near the site), then there should be a formal process to assist individuals in the evaluation of whether it contributes to the reconstruction of the trial or not.”
How to determine relevance?
Does your organization or project team provide guidance on how to determine which emails are relevant and should be filed in the TMF? ICH E6(R2) provides some helpful tips when setting relevancy criteria, but your organization may want to expand the criteria to add clarity. Additional context and examples are added in italics as suggestions to consider:
Agreements – Between two or more organizations, or persons that significantly impact the study.
Significant discussions regarding trial administration – Implementation of important changes to the trial oversight, monitoring, and study assessments. Emails that demonstrate follow-through actions should be included.
Protocol violations – Either subject-specific or significant general. Subject-specific protocol violations should include the agreed plans for dispensation of the subject.
Trial conduct – Includes subject eligibility, allowance of rescreening, and follow through actions.
Adverse event reporting – Applies to specific subject AE, pregnancy, or significant discussion of general AE management. Include evidence of follow through actions where appropriate.
Who files relevant emails in the TMF?
Once you’ve determined that an email is relevant and does need to be filed, does your organization or project team have clear guidance on who is responsible for filing it? We don’t want everyone who receives an email about the eligibility of a subject to file it in the TMF because that will result in duplicates. Will the individual who originated the email be responsible for filing it or will specific team members be asked to file the relevant emails? Are the instructions clear enough and roles understood sufficiently to avoid filing duplicate emails?
Where can you find best practices?
Does your organization or project team provide guidance on best email authoring practices? Drafting guides that add tips for writing clear and concise emails with a professional tone can be helpful. We’ve all heard the adage to think about how your email would look if it appeared on the cover of the NY Times.
What more should teams think about?
Circumstances can change quickly in a clinical trial, prompting the study team to adjust their study conduct, much like we are seeing with the current COVID-19 pandemic. While emails may be the quickest way to get essential instructions to the sites when a change is required, always remember to follow those up with updates to the formal process documents. Big or small, any changes from the previous practice, as described in the protocol, operations manual, monitoring plan, or other relevant documents, means that the team will want to update the respective procedure documents.
Emails are a valuable tool in clinical trials but can be tricky to manage. With the proper guidance and instruction, you can set your clinical trial teams up for success and ensure that only truly relevant correspondence winds up in your TMF.
ICH E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1) Guidance for Industry
MHRA online cited 02Apr2020: http://forums.mhra.gov.uk/showthread.php?1665-MHRA-produced-FAQs-for-Trial-Master-Files-(TMF)-and-Archiving